Chlamydia trachomatis is a common and important cause of sexually transmitted infection, and the most damaging diseases are salpingitis and epididymitis, that may result in infertility, chronic pelvic pain and ectopic pregnancy. The focus of this proposal is the characterization of immune responses to chlamydial infection that are related to immunity or pathogenesis. Immunity to C. trachomatis is poorly understood, although animal models and human trachoma vaccine trials have demonstrated important roles for both antibody and cell-mediated mechanisms. The hypothesis is that antigen-specific humoral and cell-mediated immune responses associated with immunity and resolution of infection can be identified using in vitro neutralization and cytotoxicity assays. Moreover, it is proposed that inflammatory pathogenic responses originate by proinflammatory cytokines produced from infected epithelial cells and amplified by antigen-specific immune responses. Over 15 serovariants of C. trachomatis have been described and serovar-specific antigens are associated with protective immunity. The major outer membrane protein (MOMP) of chlamydiae contains the serovar-specific antigen. However, this antigenically complex molecule also contains subspecies- and species-specific antigens. The MOMP is the target of antibody-mediated neutralization. The specific aims are the characterization of antibody-mediated neutralization of extracellular organisms, dissection and optimization of target MOMP epitopes, cell-mediated immune responses that recognize and lyse chlamydia-infected cells, and innate cellular immunopathogenic responses to chlamydial infection. The broad, long-term objective of this application is a basic understanding of innate and immune mechanisms associated with immune protection and disease and it is expected that this will have applications for developing a biological strategies for prevention of infection or disease.